Strategies to Prolong the Lifespan of the CRRT Circuit

Created on Sun, 07/12/2015 - 00:13
Last updated on Thu, 05/18/2017 - 19:40

Previous Chapter:

This has appeared in many previous papers.

The strategies discussed below are generic; the individual SAQs typically place the candidate in a position where they cannot use heparin (eg. the patient has HITTS).

Past paper questions on this topic have included the following:

Methods of Prolonging the CVVHDF Filter Lifespan
Strategy Advantages Disadvantages
Nothing whatsoever
(+/- regular saline flushes)
  • Circuit lifespan may still be acceptable for patients at high risk of bleeding (i.e. those who have "anticoagulated" themselves)
  • This will not benefit patients with HIT who are actually prothrombotic; another systemic anticoagulant will be required.
  • May not be suitable for patients with a normal or mildly impaired clotting function
High flow rate
  • Easy and cheap
  • Safe - no added pharmacological complications
  • Relies on a good vas cath position and a calm compliant patient.
  • The vas cath has to be reasonably widebore, which can increase the risk of vascular complications
  • The higher flow rate may not be tolerated by hemodynamically unstable patients
Pre-dilution
  • Routine and well-rehearsed modality
  • Reasonably safe in most patient groups
  • Cheap
Unfractionated heparin
  • Routine and well-rehearsed modality
  • Reasonably safe in most patient groups
  • Cheap
  • Anticoagulation is easily reversible
  • Anticoagulation is short-term
  • Does not rely on renal clearance
  • Unsuitable for HIT patients
  • May cause HIT
  • May be unsuitable for patients at high risk of bleeding
Regional anticoagulation with heparin and protamine
  • Advantageous for patients at high risk of bleeding in whom filter lifespan is still reduced due to clotting
  • Reversal of anticoagulation at the end of the circuit decreases the risk of bleeding complications
  • Unsuitable for HIT patients
  • Cumbersome protocols, greatly increased workload
  • The heparin–protamine complex is taken up
    by the reticuloendothelial system and broken down, but
    then heparin and protamine are released back into the
    circulation.
  • Protamine has known disadvantages:
    • Protamine can act as an anticoagulant
    • Protamine causes pulmonary hypertension
Low molecular weight heparin
  • More convenient (boluses vs. infusion)
  • Identical filter life to unfractionated heparin
  • May be safer in terms of bleeding risk.
  • Lower incidence of HIT
  • No need for monitoring (or, rather, monitoring is too difficult and we give up)
  •  
  • More expensive compared to unfractionated heparin
  • Clearance is renal; there is the potential for accumulation
  • May be unsafe in patients at high risk of bleeding
Warfarin
  • Cheap
  • The patient may already be warfarinised
  • No evidence for benefit in preventing catheter thrombosis
  • Difficult to initiate
  • Slow to reverse
  • Metabolism affected by numerous factors
Platelet function inhibitors:
NSAIDs, aspirin, etc
  • Difficult to monitor
  • No reversal agent - irreversible inhibition
  • Long term effects
  • Many of these drugs rely on renal clearance
Citrate
  • Reversible
  • Effective
  • Pre-mix solutions have simplified this process; protocols exist to guide the inexperienced
  • Cumbersome protocol; greatly increased workload
  • Requires frequent monitoring:
    • Sodium
    • Calcium
    • Bicarbonate (or pH)
  • If you are using trisodium citrate, you end up giving a massive amount of sodium
  • Acidosis may result due to excess citrate
  • Alkalosis may result when that citrate is metabolised
  • In hepatic failure, this is contraindicated (as citrate is metabolised mainly by the liver)
  • Special calcium-free hyponatraemic and bufferless dialysate is required
  • If the patient has HITTS, they will still require some sort of systemic anticoagulation
  • Risk of toxicity
    • High anion gap metabolic acidosis
    • Ionised hypocalcemia
Direct thrombin inhibitors:
Hirudin / Lepirudin
Bivalirudin / Argatroban
  • Alternative to heparin in HIT
  • Argatroban has a short halflife and is metabolised by the liver
  • There is a predictable near-linear relationship between hirudin levels and APTT
  • Expensive
  • Hirudin, lepirudin and bivalirudin are renally excreted; halflife will be prolonged
  • Argobatran is metabolised by the liver - halflife will be prolonged in liver failure
  • Argatroban falsely raises PT and INR.
  • All these molecules are too large to be removed by CRRT membranes, and will accumulate.
  • No reversal agent
Heparinoids (Danaparoid)
  • Expensive
  • Cross-reactivity with heparin/platelet antibodies (in 5%)
  • Long half life (48 hrs)
  • No reversal agent
  • Higher risk of bleeding than with heparin
Xa inhibitors: Fondaparinux
  • Renally cleared; may accumulate in high doses
  • Long halflife (15-20hrs)
  • No reversal agent
Serine protease inhibitors: Nafamostat
  • Suppresses neutrophil activity and may cause agranulocytosis
  • May cause increased bilirubin levels
  • Clearance relies on serum esterases, which may be decreased in chronic liver disease
  • May decrease protein C activity, leading to paradoxically increased circuit clotting
  • May cause anaphylaxis
  • May cause hyperkalemia
Prostacyclin (PGI2)
  • Very short half life (90 seconds)
  • Probably safe
  • Decreases platelet consumption in the circuit
  • Can be used together with heparin for a combined effect, as a "heparin-sparing" agent.
  • Hypotension from vasodilation
  • Ridicuously expensive
  • If the patient has HITTS, they will still require some sort of systemic anticoagulation

 

References

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